Clinical Core (Core B) ? Project Summary The Wake ADCC will focus on the hypothesis that metabolic and vascular risk factors promote the transition from normal aging to MCI, and then to AD or other forms of pathological brain aging such as vascular cognitive impairment (VCI). The Wake ADCC Clinical Core will provide resources that are pivotal to this focus, by enrolling, intensively characterizing, and following adults who are at high risk of AD due to the presence of prediabetes, a prevalent condition associated with metabolic and vascular pathology, that increases the risk of AD and other dementias. We will enroll and follow 4 groups of participants: 1) cognitively normal normoglycemic adults; 2) cognitively normal adults with prediabetes; 3) normoglycemic adults with MCI; and 4) adults with MCI and prediabetes. We will also enroll and characterize adults with AD to participate in ongoing trials, but given our focus on early transition, will not carry out intensive longitudinal phenotyping in this group. Participants will have careful longitudinal characterization, augmenting the Uniform Dataset with supplemental cognitive measures; collection and archiving of CSF, DNA, and blood; and MRI using specialized sequences to image vascular endpoints. All participants will also be approached for brain donation. A subset will receive amyloid imaging with Pittsburgh Compound B (PiB) and a novel FDG-Acetoacetate dual tracer PET scan to assess alternate fuel utilization in the brain. The Core will generate a powerful data and specimen repository that will be available to Wake investigators as well as NACC, NCRAD, and AD investigators world-wide to conduct innovative translational research on AD pathogenesis and prevention. Aim 1: To enroll and intensively characterize a cohort of cognitively normal normoglycemic or prediabetic adults, and normoglycemic or prediabetic adults with MCI, as well as participants with AD dementia who will be available for novel interventions, biomarker discovery, and genetic/epigenetic analyses, thereby exponentially expanding the scope of clinical-translational research at Wake Forest. 2: To provide resources that will determine whether Clinical Core participants with prediabetes show greater change over time on measures of cognition and AD pathology, and to explore relationships among novel AD and metabolic biomarkers and symptoms of AD, VCI, and other disorders. 3: To maximize the participation of African American adults and adults from diverse racial and ethnic backgrounds in all Center cohorts. 4: To coordinate systematic collection and archiving of brain, biospecimen, genetic, cognitive, metabolic, and imaging data that will facilitate data and specimen sharing with NACC, NCRAD, AD Centers and other collaborators. 5: To develop and collect innovative indices of metabolic and vascular risk that will be used to assess Core participants and whose protocols will be made available to investigators at Wake Forest and other institutions. These innovative methods, our unique risk-enriched cohort, and our extensive data, imaging, and biospecimen repository will enable studies to accelerate our understanding of the earliest stages of AD and other forms of pathological brain aging.